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EffECTS Of QUERCETIN AND f1 INHIBITOR ON MITOCHONDRIAL ATPASE AND ENERGY-LINKED REACTIONS IN SUBMITOCHONDRIAL PARTICLES

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BIOCHIMICA ET BIOPHYSICA ACTA 1974年第2期333卷 180-186页

作者： LANG, DR RACKER, E CORNELL UNIV SECT BIOCHEM MOLECUL & CELL BIOLITHACANY 14850

Quercetin (3,3′,4′,5,7-pentahydroxyflavone) shares certain properties with the mitochondrial ATPase inhibitor protein. At low concentrations it inhibits both soluble and particulate mitochondrial ATPase and has no effect on oxidative phosphorylation in submitochondrial particles. Unlike the mitochondrial inhibitor protein quercetin inhibits the ATP-dependent reduction of NAD + by succinate in fully reconstituted submitochondrial particles. A comparison of various flavones indicates that the hydroxyl groups at the 3′ and perhaps 3 position are important for the inhibition of ATPase activity.

关键词： f 1 coupling factor 1 (ATPase) A particles (EDTA particles) submitochondrial particles prepared by sonication of beef heart mitochondria in the presence of ammonia and EDTA

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Week 96 subgroup analyses of the phase 3, randomized AMBER and EMERALD trials evaluating the efficacy and safety of the once daily darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/f/TAf) single-tablet regimen in antiretroviral treatment (ART)-naive and -experienced, virologically-suppressed adults living with HIV-1

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HIV RESEARCH & CLINICAL PRACTICE 2021年第6期21卷 151-167页

作者： Huhn, Gregory D. Wilkin, Aimee Mussini, Cristina Spinner, Christoph D. Jezorwski, John El Ghazi, Mohsine Van Landuyt, Erika Lathouwers, Erkki Brown, Kimberley Baugh, Bryan Ruth M Rothstein CORE Ctr 2020 W Harrison St Chicago IL 60612 USA Wake Forest Sch Med Sect Infect Dis Winston Salem NC 27101 USA Univ Modena & Reggio Emilia Dept Infect Dis Modena Italy Tech Univ Munich Sch Med Munich Germany Janssen Res & Dev LLC Pennington NJ USA Janssen Pharmaceut NV Beerse Belgium Janssen Res & Dev LLC Raritan NJ USA

Background Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/f/TAf) 800/150/200/10 mg was investigated in AMBER (treatment-naive adults;NCT02431247) and EMERALD (treatment-experienced, virologically-suppressed adults;NCT02269917). Objective To describe a Week 96 pre-planned subgroup analysis of D/C/f/TAf arms by demographic characteristics (age <=/>50 years, gender, black/non-black race), and baseline clinical characteristics (AMBER: viral load [VL], CD4(+) count, WHO clinical stage, HIV-1 subtype and antiretroviral resistance;EMERALD: prior virologic failure [Vf], antiretroviral experience, screening boosted protease inhibitor [PI], and boosting agent). Methods Patients in D/C/f/TAf and control arms could continue on/switch to D/C/f/TAf in a single-arm, open-label extension phase after Week 48 until Week 96. Efficacy endpoints were percentage cumulative confirmed VL >= 50 copies/mL (virologic rebound;EMERALD), and VL <50 (virologic response), or >= 50 copies/mL (Vf) (fDA snapshot;both trials). Results D/C/f/TAf demonstrated high Week 96 virologic responses (AMBER: 85% [308/362];EMERALD: 91% [692/763]) and low Vf rates (AMBER: 6% [20/362];EMERALD: 1% [9/763]). In EMERALD, D/C/f/TAf showed low virologic rebound cumulative through Week 96 (3% [24/763]). Results were consistent across subgroups, including prior antiretroviral experience in EMERALD. No darunavir, primary PI, or tenofovir resistance-associated mutations were observed post-baseline. Study-drug-related serious adverse events (AEs) and AE-related discontinuations were <1% and 2%, respectively (both D/C/f/TAf arms), and similar across subgroups. eGfR(cyst) and bone mineral density improved or were stable and lipids increased through Week 96 across demographic subgroups, with small changes in total-cholesterol/HDL-cholesterol ratio. Conclusions D/C/f/TAf was effective with a high barrier to resistance and bone/renal safety benefits, regardless of demographic or clinical characteristics for treatme

关键词： D C f TAf HIV-1 darunavir single-tablet regimen tenofovir alafenamide subgroup analysis Phase III

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Catalytic degradation of methylene blue by biosynthesised copper nanoflowers using f-benghalensis leaf extract

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IET NANOBIOTECHNOLOGY 2016年第5期10卷 321-325页

作者： Agarwal, Meenakshi Bhadwal, Akhshay Singh Kumar, Nishant Shrivastav, Archana Shrivastav, Braj Raj Singh, Manoj Pratap Zafar, fahmina Tripathi, Ravi Mani Amity Univ Amity Inst Nanotechnol Sect 125 Noida 201303 UP India Coll Life Sci Dept Microbiol Gwalior 474009 MP India Canc Hosp & Res Inst Dept Surg Oncol Gwalior 474009 MP India GR Med Coll Dept Surg Palace Rd Gwalior 474009 MP India Jawaharlal Nehru Univ Adv Instrumentat Res Facil New Delhi 110067 India Jamia Millia Islamia Dept Chem Inorgan Mat Res Lab New Delhi 110025 India

This study reports the unprecedented, novel and eco-friendly method for the synthesis of three-dimensional (3D) copper nanostructure having flower like morphology using leaf extract of ficus benghalensis. The catalytic activity of copper nanoflowers (CuNfs) was investigated against methylene blue (MB) used as a modal dye pollutant. Scanning electron micrograph evidently designated 3D appearance of nanoflowers within a size range from 250 nm to 2.5 m. Energy-dispersive X-ray spectra showed the presence of copper elements in the nanoflowers. fourier-transform infrared spectra clearly demonstrated the presence of biomolecules which is responsible for the synthesis of CuNfs. The catalytic activity of the synthesised CuNfs was monitored by ultraviolet-visible spectroscopy. The MB was degraded by 72% in 85 min on addition of CuNfs and the rate constant (k) was found to be 0.77 x 10(-3) s(-1). This method adapted for synthesis of CuNfs offers a valuable contribution in the area of nanomaterial synthesis and in water research by suggesting a sustainable and an alternative route for removal of toxic solvents and waste materials.

关键词： catalysis dyes nanostructured materials nanofabrication scanning electron microscopy X-ray chemical analysis copper fourier transform infrared spectra visible spectra ultraviolet spectra molecular biophysics catalytic degradation methylene blue biosynthesised copper nanoflowers f benghalensis leaf extract three-dimensional copper nanostructure synthesis 3D copper nanostructure synthesis flower like morphology ficus benghalensis leaf extract modal dye pollutant electron micrograph 3D appearance energy-dispersive X-ray spectra copper elements fourier-transform infrared spectra biomolecules ultraviolet-visible spectroscopy toxic solvent removal waste materials size 250 nm to 2 5 mum Cu

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f. prausnitzii and its supernatant increase SCfAs-producing bacteria to restore gut dysbiosis in TNBS-induced colitis

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AMB EXPRESS 2021年第1期11卷 33页

作者： Zhou, Youlian Xu, Haoming Xu, Jing Guo, Xue Zhao, Hailan Chen, Ye Zhou, Yongjian Nie, Yuqiang South China Univ Technol Dept Gastroenterol Guangzhou Peoples Hosp 1 Guangzhou Digest Dis CtrSch Med 1 Panfu Rd Guangzhou 510180 Peoples R China Southern Med Univ Dept Gastroenterol Nanfang Hosp Guangzhou 510515 Peoples R China

An increasing number of studies have shown that faecalibacterium prausnitzii (f. prausnitzii) is a promising anti-inflammatory bacterium that colonizes in the gut and that gut microbiota dysbiosis plays an important role in the pathogenesis of inflammatory bowel disease (IBD). In this study, we report the gut microbiota profile of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis mice treated with f. prausnitzii and its supernatant on the basis of high-throughput sequencing. We interestingly found that both f. prausnitzii and its metabolites exerted protective effects against colitis in mice, which ameliorated gut dysbiosis, with an increase in bacterial diversity and the abundance of short-chain fatty acid (SCfA)-producing bacteria and a decrease in serum TNf-alpha and the abundance of Proteinbacteria, Acidobacteria, and Bacteroidetes. These findings will provide further evidence of the anti-inflammatory effect of f. prausnitzii, which presents therapeutic potential for IBD treatment.

关键词： Inflammatory bowel disease Gut microbiota f prausnitzii Supernatant Short chain fatty acid

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EffICIENT RECONSTITUTION Of MITOCHONDRIAL ENERGY-TRANSfER REACTIONS fROM DEPLETED MEMBRANES AND f1-ATPASE AS A fUNCTION Of THE AMOUNT Of BOUND OLIGOMYCIN SENSITIVITY-CONfERRING PROTEIN (OSCP)

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BIOCHIMICA ET BIOPHYSICA ACTA 1986年第1期852卷 55-67页

作者： PENIN, f DELEAGE, G GODINOT, C GAUTHERON, DC Laboratoire de Biologie et Technologie des Membranes du Centre National de la Recherche Scientifique Université Claude Bernard de Lyon 43 Boulevard du 11 novembre 1918 69622 Villeurbanne Cedex France

(1) Pig heart mitochondrial membranes depleted of f1 and OSCP by various treatments were analyzed for their content in .alpha. and .beta. subunits of f1 and in OSCP using monoclonal antibodies. Membrane treatments and conditions of rebinding of f1 and OSCP were optimized to reconstitute efficient NADH- and ATP-dependent proton fluxes, ATP synthesis and oligomycin-sensitive ATPase activity. (2) f1 and OSCP can be rebound independently to depleted membranes but to avoid unspecific binding of f1 to depleted membranes (ASUA) which is not efficient for ATP synthesis, f1 must be rebound before the addition of OSCP. (3) The rebinding of OSCP to depleted membranes reconstituted with f1 inhibits the ATPase activity of rebound f1, while it restores the ATP-driven proton flux measured by the quenching of ACMA fluorescence. The rebinding of OSCP also renders the ATPase activity of bound f1 sensitive to uncouplers. (4) The rebinding of OSCP alone or f1 alone, does not modify the NADH-dependent proton flux, while the rebinding of both f1 and OSCP controls this flux, inducing an inhibition of the rate of NADH oxidation. Similarly, oligomycin, which seals the f0 channel even in the absence of f1 and OSCP, inhibits the rate of NADH oxidation. (5) OSCP is required to adjust the fitting of f1 to f0 for a correct channelling of protons efficient for ATP synthesis. (6) All reconstituted energy transfer reactions rearch their optimal value for the same amount of OSCP. This amount is consistent with a stoichiometry of two OSCP per f1 in the f0-f1 complex.

关键词： Oligomycin sensitivity-conferring protein f 1 -ATPase Proton translocation ATP synthesis NADH oxidation (Pig heart mitochondria) ETP inverted submitochondrial particles f 1 nucleotide-depleted pig-heart mitochondrial ATPase OSCP oligomycin sensitivity-conferring protein ASUA particles ASU particles treated with NH 3 to remove OSCP ASU particles submitochondrial particles treated with ammonia, Sephadex and urea to remove f 1 ATPase adenosine-5′-triphosphatase (EC 3.6.1.3) ACMA 9-amino-6-chloro-2-methoxy-acridine IODOGEN 1,3,4,6-tetrachloro-3α,6α-diphenylglycoluril NEM N -ethylmaleimide fCCP carbonylcyanide p -trifluoromethoxyphenylhydrazone EDTA ethylenediaminetetraacetic acid Tris 2-amino-2-hydroxymethylpropane-1,3-diol Mes 4-morpholineethanesulphonic acid Hepes 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid P i inorganic phosphate

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DNA ADDUCT fORMATION Of THE CARCINOGEN 2-AMINO-3-METHYLIMIDAZO[4,5-f]-QUINOLINE IN TARGET TISSUES Of THE f-344-RAT

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CANCER LETTERS 1988年第3期41卷 345-352页

作者： SCHUT, HAJ PUTMAN, KL RANDERATH, K BAYLOR COLL MED DEPT PHARMACOL HOUSTON TX 77030 USA

2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), a potent bacterial mutagen present in broiled sardines, cooked beef and beef extract, is a carcinogen in the f-344 rat, affecting mainly the liver and small and large intestines. Using 32P-postlabeling assays, the formation of IQ-DNA adducts was examined in male f-344 rats. Twenty-four hours after i.p. doses (5-50 mg IQ/kg) the liver, small and large intestine each showed the presence of 5 adducts, the liver and large intestine having an average of 18.1 and 2.4 times as many adducts, respectively, as the small intestine. None of these adducts could be detected in vehicle-treated animals. It is concluded that IQ forms specific DNA adducts in target tissues of the f-344 rat.

关键词： 2-Amino-3-methylimidazo[4,5- f ]quinoline DNA adducts 32 P-postlabeling fischer-344 rats food mutagens Heterocyclic amines

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DETECTION Of NEW METABOLITES Of TRIfLURIDINE (f3TDR) USING f-19 NMR-SPECTROSCOPY

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BIOCHEMICAL PHARMACOLOGY 1992年第11期44卷 2223-2228页

作者： TANDON, M KUMAR, P WIEBE, G WIEBE, LI UNIV ALBERTA FAC PHARM & PHARMACEUT SCIEDMONTON T6G 2N8ALBERTACANADA

The metabolism of 5-trifluoromethyl-2'-deoxyuridine (trifluridine, f3TdR) in male BALB/C mice has been studied by f-19 NMR spectroscopy. Contrary to previous reports, a number of fluorinated metabolites were observed in urine, whole livers and blood samples taken from mice after i.p. injection of f3TdR. The present study describes the identification of two new metabolites in mouse urine using the f-19 NMR technique. The NMR of crude urine showed the presence of f3TdR, 5-trifluorothymine (f3T), the newly-identified metabolites, 5-trifluoromethyl-5,6-dihydrouracil (DHf3T) and 5-trifluoromethyl-5,6-dihydroxyuracil (DOHf3T), and several new, as yet unidentified fluorinated metabolites. These two new metabolites were characterized by comparison to authentic compounds prepared synthetically from f3T.

关键词： f 3 TdR 5-trifluoromethyl-2′-deoxyuridine f 3 T 5-trifluorothymine DHf 3 T 5-trifluoromethyl-5, 6-dihydrouracil DOHf 3 T 5-trinuoromethyl-5, 6-dihydroxyuracil f 3 TdRP, 5-trifluoromethyl-2′-deoxyuridine-5′-phosphate fUdR 5-fluoro-2′-deoxyuridine f 3 TBA α-trifluoromethyl-β-alanine f 3 TUPA trifluoromethyluriedopropionic acid

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STUDIES Of THE NUCLEOTIDE-BINDING SITES ON THE MITOCHONDRIAL-f1-ATPASE THROUGH THE USE Of A PHOTOACTIVABLE DERIVATIVE Of ADENYLYL IMIDODIPHOSPHATE

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BIOCHIMICA ET BIOPHYSICA ACTA 1982年第1期682卷 124-134页

作者： LUNARDI, J VIGNAIS, PV Laboratoire de Biochimie (CNRS/ERA 903 et INSERM/U.191) Départment de Recherche Fondamentale Centre d'Etudes Nucléaires 85X 38041 Grenoble cedex France

N-4-Azido-2-nitrophenyl-.gamma.-[3H]-aminobutyryl-AdoPP[NH]P (NAP4-AdoPP[NH]P) a photoactivable derivative of 5-adenylyl imidodiphosphate (AdoPP[NH]P), was synthesized. Binding of [3H]NAP4-AdoPP[NH]P to soluble ATPase from beef heart mitochondria (f1) was studied in the absence of photoirradiation, and compared to that of [3H]AdoPP[NH]P. The photoactivable derivative of AdoPP[NH]P bound to f1 with high affinity, like AdoPP[NH]P. Once [3H]NAP4-AdoPP[NH]P had bound to f1 in the dark, it could be released by AdoPP[NH]P, ADP and ATP, but not at all by NAP4 or AMP. Preincubation of f1 with unlabeled AdoPP[NH]P, ADP or ATP prevented the covalent labeling of the enzyme by [3H]NAP4-AdoPP[NH]P on photoirradiation. Photoirradiation of f1 by [3H]NAP4-AdoPP[NH]P resulted in covalent photolabeling and concomitant inactivation of the enzyme. full inactivation corresponded to the binding of .apprx. 2 mol [3H]NAP4-AdoPP[NH]P/mol f1. Photolabeling by NAP4-AdoPP[NH]P was much more efficient in the presence than in the absence of MgCl2. Bound [3H]NAP4-AdoPP[NH]P was localized on the .alpha.- and .beta.-subunits of f1. At low concentrations (< 10 .mu.M), bound [3H]NAP4-AdoPP[NH]P was predominantly localized on the .alpha.-subunit;at concentrations equal to, or greater than 75 .mu.M, .alpha.- and .beta.-subunits were equally labeled. The extent of inactivation was independent of the nature of the photolabeled subunit (.alpha. or .beta.), suggesting that each of the 2 subunits, .alpha. and .beta., is required for the activity of f1. The covalently photolabeled f1 was able to form a complex with aurovertin, as does native f1. The ADP-induced fluorescence enhancement was more severely inhibited than the fluorescence quenching caused by ATP. The percentage of inactivation of f1 was virtually the same as the percentage of inhibition of the ATP-induced fluorescence quenching, suggesting that fluorescence quenching is related to the binding of ATP to the catlytic site of f1.

关键词： Nucleotide binding f 1 -ATPase Adenylyl imidodiphosphate Photolabeling (Bovine heart mitochondria) f 1 , soluble mitochondrial ATPase from beef heart mitochondria Ado PP [NH] P , 5-adenylyl imidodiphosphate NAP 4 , N -4-azido-2-nitrophenyl- γ -aminobutyric acid NAP 4 -Ado PP [NH] P , N -4-azido-2-nitrophenyl- γ -aminobutyryl-Ado PP [NH] P NAP 4 -ADP, N -4-azido-2-nitrophenyl- γ -aminobutyryl-ADP

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INTERACTION Of ESCHERICHIA-COLI f1-ATPASE WITH DICYCLOHEXYLCARBODIIMIDE-BINDING POLYPEPTIDE

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BIOCHIMICA ET BIOPHYSICA ACTA 1983年第2期733卷 274-282页

作者： LOO, TW STANLOTTER, H MACKENZIE, D MOLDAY, RS BRAGG, PD UNIV BRITISH COLUMBIA DEPT BIOCHEM VANCOUVER V6T 1W5 BC CANADA

Antibody raised against the N,N''-dicyclohexylcarbodiimide (DCCD)-binding polypeptide of E. coli bound to the cytoplasmic surface of the cell membrane. A weak reaction was seen with everted vesicles of the thermophile PS3. Rat liver mitochondrial membranes did not react with the antibody. Reaction of the isolated DCCD-binding polypeptide with the antibody was prevented by oxidation of methionine residues or cleavage of the polypeptide with CNB. Modification of the arginine residues of the DCCD-binding polypeptide did not affect interaction with the antibody. Purified f1-ATPase of E. coli bound to the isolated DCCD-binding polypeptide as shown by solid-phase radioimmune assay. Binding involved the .alpha. and/or .beta. subunits of f1 and the arginine residues of the polar central region of the DCCD-binding polypeptide. The results are consistent with a looped arrangement of the DCCD-binding polypeptide in the membrane in which the carboxyl- and amino-terminal regions of the molecule are at the periplasmic surface and the polar central region, interacting with f1, is at the cytoplasmic surface of the cell membrane.

关键词： f 1 -ATPase Dicyclohexylcarbodiimide-binding polypeptide Protein orientation ( E. coli ) DCCD N,N 1 - dicyclohexylcarbodiimide f 1 f 1 -ATPase protein of the ATPase complex f 0 f 0 protein of the ATPase complex

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REACTION Of MEMBRANE-BOUND f1-ADENOSINE TRIPHOSPHATASE Of ESCHERICHIA-COLI WITH CHEMICAL LIGANDS AND THE ASYMMETRY Of BETA-SUBUNITS

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BIOCHIMICA ET BIOPHYSICA ACTA 1990年第2期1015卷 216-222页

作者： BRAGG, PD HOU, C Department of Biochemistry Univ. of British Columbia 2146 Health Sciences Mall Vancouver BC Canada

The three .beta. subunits of the isolated Escherichia coli f1-ATPase react independently with chemical reagents (Stan-Lotter, H. and Bragg P.D. (1986) Arch. Biochem. Biophys. 284, 116-120). Thus, one .beta. subunit is readily cross-linked to the .epsilon. subunit. Another reacts with N,N''-dicyclohexylcarbodiimide (DCCD), and the third one is modified on a lysine residue by 4-chloro-7-nitrobenzofurazan (NbfCl). The binding site for the ATP analog, 2-azido-ATP, was not associated with a specific type of .beta. subunit (Bragg, P.D. and Hou, C. (1989) Biochim. Biophys. Acta 974, 24-29). We now show that this binding site is a catalytic site as opposed to a noncatalytic nucleotide-binding site. NbfCl reacted with a tyrosine residue on the DCCD-reacting .beta. subunit in contrast to the different subunit location of the lysine residue labeled by the reagent. Thus, O to N transfer of the Nbf group in the free f1-ATPase involves transfer between subunits. The chemical labelling pattern of membrane-bound f1-ATPase differed from that of free f1. The strict asymmetry of labeling of the free f1-ATPase was not observed. Thus, double labeling of .beta. subunits by several reagents was found. This suggest that the asymmetry was not induced by chemical modification, but is inherent in the structure of the ATPase.

关键词： (E. coli) ATPase Beta subunit Chemical modification 2-Azido-ATP f 1 -

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